An Extension Study for Subjects Who Are Deriving Benefit With Idelalisib (GS-1101; CAL-101) Following Completion of a Prior Idelalisib StudyRecruiting

This is a long-term safety extension study of idelalisib (GS-1101; CAL-101) in patients with
hematologic malignancies who complete other idelalisib studies. It provides the opportunity
for patients to continue treatment as long as the patient is deriving clinical benefit.
Patients will be followed according to the standard of care as appropriate for their type of
cancer. The dose of idelalisib will generally be the same as the dose that was administered
at the end of the prior study, but may be titrated up to improve clinical response or down
for toxicity. Patients will be withdrawn from the study if they develop progressive disease,
unacceptable toxicity related to idelalisib, or if they no longer derive clinical benefit in
the opinion of the investigator.

Safety Study of CAT-8015 Immunooxin in Patients With HCL With Advance DiseaseNot Recruiting

RATIONALE: The CAT-8015 immunotoxin can bind tumor cells and kill them without harming
normal cells. This may be an effective treatment for hairy cell leukemia(HCL) that has not
responded to chemotherapy, surgery or radiation therapy.
PURPOSE: Phase I dose escalation study to determine the maximum tolerated dose of CAT-8015
immunotoxin in treating patients who have hairy cell leukemia (HCL) that has not responded
to treatment.

Stanford is currently not accepting patients for this trial.For more information, please contact Michelle Takahashi, (650) 736 - 4032.

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer
cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies,
such as gemtuzumab, can block cancer growth in different ways. Some find cancer cells and
help kill them or carry cancer-killing substances to them. Others interfere with the ability
of cancer cells to grow and spread. Gemtuzumab may also stop the growth of promyelocytic
leukemia by blocking blood flow to the cancer. Giving gemtuzumab together with combination
chemotherapy may be more effective in treating promyelocytic leukemia.
PURPOSE: This phase II trial is studying how well giving gemtuzumab together with
combination chemotherapy works in treating patients with previously untreated promyelocytic
leukemia.

Stanford is currently not accepting patients for this trial.For more information, please contact Nini Estevez, (650) 725 - 4041.

The purpose of this study is to evaluate the safety of lenalidomide and to define the
maximum tolerated escalation dose level (MTEDL) when administered by a stepwise
dose-escalation schedule in subjects with relapsed or refractory B-cell CLL.

Stanford is currently not accepting patients for this trial.For more information, please contact Michelle Takahashi, (650) 736 - 4032.

This phase II trial is studying the side effects of giving azacitidine together with
gemtuzumab ozogamicin to see how well it works in treating older patients with previously
untreated acute myeloid leukemia. Drugs used in chemotherapy, such as azacitidine, work in
different ways to stop the growth of cancer cells, either by killing the cells or by
stopping them from dividing. Azacitidine may also stop the growth of cancer cells by
blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as
gemtuzumab ozogamicin, can block cancer growth in different ways. Some block the ability of
cancer cells to grow and spread. Others find cancer cells and help kill them or carry
cancer-killing substances to them. Giving azacitidine together with gemtuzumab ozogamicin
may kill more cancer cells.

Stanford is currently not accepting patients for this trial.For more information, please contact Joselene Sipin-Sayno, (650) 736 - 8113.

RATIONALE: Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different
ways to stop the growth of cancer cells, either by killing the cells or by stopping them
from dividing. Pravastatin may stop the growth of cancer cells by blocking some of the
enzymes needed for cell growth. Pravastatin may also help idarubicin and cytarabine work
better by making cancer cells more sensitive to the drugs. Giving idarubicin and cytarabine
together with pravastatin may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving idarubicin and cytarabine together
with pravastatin works in treating patients with relapsed acute myeloid leukemia.

RATIONALE: Monoclonal antibodies, such as epratuzumab, can block cancer growth in different
ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells
and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy,
such as cytarabine and clofarabine, work in different ways to stop the growth of cancer
cells, either by killing the cells or by stopping them from dividing. Giving epratuzumab
together with cytarabine and clofarabine may kill more cancer cells.
PURPOSE: This phase II trial is studying the side effects and how well giving epratuzumab
together with cytarabine and clofarabine works in treating patients with relapsed or
refractory acute lymphoblastic leukemia.

Stanford is currently not accepting patients for this trial.For more information, please contact Nini Estevez, (650) 725 - 4041.

The purpose of this study is to evaluate the safety and clinical activity of idelalisib in
combination with CD20 mAb chemotherapeutic agents, Immunomodulatory Agents, mTOR inhibitors
and proteasome inhibitor in participants with hematologic malignancies.

The purpose of this study is to compare the effects, good and/or bad, of a standard
chemotherapy regimen for AML that includes the drugs daunorubicin and cytarabine combined
with or without midostaurin (also known as PKC412), to find out which is better. This
research is being done because it is unknown whether the addition of midostaurin to
chemotherapy treatment is better than chemotherapy treatment alone. Midostaurin has been
tested in over 400 patients and is being studied in a number of illnesses, including AML,
colon cancer, and lung cancer. Midostaurin blocks an enzyme, produced by a gene known as
FLT3, that may have a role in the survival and growth of AML cells. Not all leukemia cells
will have the abnormal FLT3 gene. This study will focus only on patients with leukemia cells
with the abnormal FLT3 gene.

Stanford is currently not accepting patients for this trial.For more information, please contact Leonel Gallegos, (650) 723 - 2781.

This is a Phase II, open-label, non-randomized study to evaluate the safety, efficacy, and
pharmacokinetics of tamibarotene in adult patients with relapsed or refractory acute
promyelocytic leukemia (APL) following treatment with all-trans-retinoic acid (ATRA) and
arsenic trioxide (ATO). Patients must have received and failed therapy with ATRA and ATO.
Treatment may have been administered either as combination therapy or sequentially as single
agents. Patients who are intolerant to either drug are eligible for this study.

Stanford is currently not accepting patients for this trial.For more information, please contact Michelle Takahashi, (650) 736 - 4032.

This Phase 3, randomized, double-blind, placebo-controlled study is to evaluate the effect
of idelalisib in combination with rituximab on the onset, magnitude, and duration of tumor
control in participants previously treated for chronic lymphocytic leukemia (CLL). Eligible
patients will be randomized with a 1:1 ratio into 1 of the 2 treatment arms to receive
either idelalisib plus rituximab or placebo plus rituximab. Participants who are tolerating
primary study therapy but experience definitive CLL progression are eligible to receive
active idelalisib therapy in the extension study, GS-US-312-0117.

Stanford is currently not accepting patients for this trial.For more information, please contact Tessa Hunter, (650) 736 - 4032.

Extension Study of Idelalisib for Patients With Chronic Lymphocytic Leukemia Who Participated in GS-US-312-0116Not Recruiting

This study (GS-US-312-0117) is a multicenter, 2-arm, double-blind, parallel-group extension
study that is a companion study to Study GS-US-312-0116, to evaluate the effect of
idelalisib on the onset, magnitude, and duration of tumor control.

Stanford is currently not accepting patients for this trial.For more information, please contact Tessa Hunter, (650) 736 - 4032.

This phase II trial is studying the side effects of giving combination chemotherapy together
with or without donor stem cell transplant and to see how well it works in treating patients
with acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop
the growth of cancer cells, either by killing the cells or by stopping them from dividing.
Giving more than one drug (combination chemotherapy) may kill more cancer cells. Giving
chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the
growth of cancer cells. It also stops the patient's immune system from rejecting the donor's
stem cells. The donated stem cells may replace the patient's immune cells and help destroy
any remaining cancer cells (graft-versus-tumor effect).

Stanford is currently not accepting patients for this trial.For more information, please contact Vani Jain, (650) 725 - 5459.

The purpose of this study is to evaluate the efficacy and safety of idelalisib in patients
with previously treated indolent Non-Hodgkin Lymphoma (iNHL) that is refractory both to
rituximab and to alkylating-agent-containing chemotherapy. The primary objective will be to
assess the overall response rate.
Eligible patients will initiate oral therapy with idelalisib at a starting dose of 150 mg
taken twice per day. Treatment with idelalisib can continue in compliant patients as long
as the study is still ongoing and the patients appear to be benefiting from treatment with
acceptable safety.

Stanford is currently not accepting patients for this trial.For more information, please contact Tessa St.Rose, (650) 736 - 4032.

The main objective of this study is to learn which sapacitabine treatment is more likely to
keep the cancer in check for at least one year in AML patients who are at least 70 years of
age or older and in MDS patients who are at least 60 years of age.

Stanford is currently not accepting patients for this trial.For more information, please contact Michelle Takahashi, (650) 736 - 4032.

A Study of Idelalisib and Rituximab in Elderly Patients With Untreated CLL or SLLNot Recruiting

This study is to evaluate the safety and clinical activity of idelalisib alone and in
combination with rituximab in patients with CLL or SLL.
This Phase 2 study will be the first time that idelalisib is administered to previously
untreated patients with hematologic malignancies. Idelalisib has demonstrated clinical
activity as a single agent in relapsed or refractory CLL and SLL with acceptable toxicity,
which supports its evaluation in previously untreated patients. The study population is
limited to patients over 65 years of age because younger patients are generally appropriate
for standard immunochemotherapy regimens that are highly active. Since the mechanism of
action of idelalisib is distinct from rituximab, it is hypothesized that the combination
will be more active than either agent alone. This study will establish initial safety and
clinical activity of idelalisib in combination with rituximab in patients with CLL or SLL.
Cohort 2 of this study will establish safety and clinical activity of idelalisib alone in
subjects with untreated CLL or SLL.

Stanford is currently not accepting patients for this trial.For more information, please contact Nini Estevez, (650) 725 - 4041.

The purpose of this study is to determine if the use of adjunctive Pharmacomechanical
Catheter Directed Thrombolysis, which includes the intrathrombus administration of
rt-PA--Activase (Alteplase),can prevent the post-thrombotic syndrome(PTS)in patients with
symptomatic proximal deep vein thrombosis(DVT)as compared with optimal standard DVT therapy
alone.

Abstract

There are limited treatment options for older patients with acute myeloid leukemia and prognosis of these patients remains poor, thereby warranting development of novel therapies. We evaluated the efficacy and safety of azacitidine in combination with lenalidomide as front-line therapy for older patients with acute myeloid leukemia. Patients ≥ 60 years of age with untreated acute myeloid leukemia received azacitidine 75 mg/m2 for 7 days followed by escalating doses of lenalidomide daily for 21 days starting on day 8 of each cycle every 6 weeks. Patients received continued therapy until disease progression, unacceptable toxicity, or completion of 12 cycles. Forty-two patients (median age, 74 years) were enrolled with equal distribution according to European LeukemiaNet risk. The overall response rate was 40% (rate of complete remission with or without complete recovery of blood counts = 28%). The median time to complete remission with or without complete recovery of blood counts was 12 weeks, and duration of this status was 28 weeks (range, 4 - >104 weeks). Therapy-related acute myeloid leukemia and a high score on the Hematopoietic Cell Transplantation Comorbidity Index were negative predictors of response. Early death was noted in 17% of patients. Grades ≥ 3 toxicities were uncommon and most adverse events were gastrointestinal, fatigue and myelosuppression. In conclusion, a sequential combination of azacitidine plus lenalidomide has clinical activity in older patients with acute myeloid leukemia, and further studies of this combination are underway.

Abstract

Acute myeloid leukemia (AML) is a disease of the elderly. Poor outcomes with standard therapies necessitate novel approaches. Outpatient regimens sufficiently potent and well tolerated to induce remissions and enable continuation therapy may be beneficial. In this phase-1 study, we determined the maximum tolerated dose (MTD) and the efficacy for sequential azacitidine and lenalidomide as remission induction and continuation therapy in elderly, previously untreated patients. We investigated the impact on global DNA methylation and bone marrow cytokines, and sought biological predictors of response. Eighteen patients were enrolled. The MTD was not reached. Median follow-up was 8.2 months (10.3 months for survivors). Common adverse events included fatigue, injection site reactions, constipation, nausea, pruritus and febrile neutropenia. Ten patients responded (56%), and the rate of complete remissions (CRs) or CRs with incomplete recovery of blood counts for evaluable patients was 44% (7/16). The median response duration was 6.2 months. DNA demethylation and changes in bone marrow cytokines were observed; responders had a unique cytokine profile and a trend towards lower methylation levels. Sequential azacitidine and lenalidomide was well tolerated with encouraging clinical and biological activity in previously untreated elderly AML patients. This trial is registered at ClinicalTrials.gov (NCT00890929).

Abstract

This phase I trial was conducted to determine the safety and pharmacokinetics of monoclonal antibody 216, a human monoclonal Immunoglobulin M antibody targeting a linear B-cell lactosamine antigen, administered alone and in combination with vincristine in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, and to preliminarily assess tumor targeting and efficacy.Three cohorts of patients received escalating doses of monoclonal antibody 216 administered as an intravenous infusion. In the case of poor response to the first dose of monoclonal antibody 216 alone, defined as less than 75% reduction in peripheral blood blast count, a second dose of the antibody with vincristine was given between days 4 and 7. Responses were assessed weekly until day 35. Serum concentration of monoclonal antibody 216 was measured before and after infusion. Monoclonal antibody 216 targeting was determined with an anti-idiotypic antibody to monoclonal antibody 216 and preliminary efficacy was analyzed by changes in peripheral blood blasts.Thirteen patients were enrolled. One episode of grade 3 epistaxis was the only dose-limiting toxicity observed. All patients showed a poor response to the first monoclonal antibody 216 infusion with a decrease in peripheral blasts from 6-65% in 9 patients. In 8 patients, addition of vincristine to monoclonal antibody 216 resulted in an average reduction of the peripheral blasts of 81%. One patient without peripheral blasts achieved a hypoplastic marrow without evidence of leukemia after one infusion of monoclonal antibody 216 and monoclonal antibody 216/vincristine each. Monoclonal antibody 216 was detected on peripheral blasts in all patients.Treatment with monoclonal antibody 216 in combination with vincristine is feasible and well tolerated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Binding of monoclonal antibody 216 to leukemic blasts was efficient, and favorable early responses were observed.

Abstract

The case of a patient receiving long-term anticoagulation with warfarin who had supratherapeutic International Normalized Ratios (INRs) after receiving concomitant acetaminophen and moxifloxacin as prophylaxis with bacille Calmette-Guérin (BCG) therapy for bladder cancer is reported.An 89-year-old man receiving long-term anticoagulation with warfarin sodium (total weekly dosage of 19 mg) arrived at the anticoagulation clinic for his monthly visit. On the day before this visit, he had received the third of six serial weekly BCG bladder instillations for the treatment of bladder cancer. He did not report that acetaminophen 1000 mg four times daily and one dose of moxifloxacin 400 mg had been prescribed before these instillations. An INR check revealed a value of 6.7. He was instructed to take 2.5 mg of oral phytonadione and to withhold his warfarin dose that night. On the next day, his INR was 3.2. Each time he arrived at the anticoagulation clinic after his BCG therapy, his INR was supratherapeutic, except after his fourth treatment (INR of 2.5), which can be explained by residual effects from the phytonadione he received a week earlier. After completion of his BCG therapy, he was instructed to resume his usual warfarin sodium dosage of 19 mg weekly, and his INR remained in the desired therapeutic range. According to the Drug Interaction Probability Scale, the development of supratherapeutic INRs was probably associated with concomitant acetaminophen and moxifloxacin use.An 89-year-old man receiving long-term anticoagulation with warfarin had supratherapeutic INRs after receiving acetaminophen and moxifloxacin as prophylaxis during BCG therapy for bladder cancer.

Abstract

Warfarin dosing remains challenging because of its narrow therapeutic window and large variability in dose response. We sought to analyze new factors involved in its dosing and to evaluate eight dosing algorithms, including two developed by the International Warfarin Pharmacogenetics Consortium (IWPC).we enrolled 108 patients on chronic warfarin therapy and obtained complete clinical and pharmacy records; we genotyped single nucleotide polymorphisms relevant to the VKORC1, CYP2C9, and CYP4F2 genes using integrated fluidic circuits made by Fluidigm.When applying the IWPC pharmacogenetic algorithm to our cohort of patients, the percentage of patients within 1 mg/d of the therapeutic warfarin dose increases from 54% to 63% using clinical factors only, or from 38% using a fixed-dose approach. CYP4F2 adds 4% to the fraction of the variability in dose (R) explained by the IWPC pharmacogenetic algorithm (P<0.05). Importantly, we show that pooling rare variants substantially increases the R for CYP2C9 (rare variants: P=0.0065, R=6%; common variants: P=0.0034, R=7%; rare and common variants: P=0.00018; R=12%), indicating that relatively rare variants not genotyped in genome-wide association studies may be important. In addition, the IWPC pharmacogenetic algorithm and the Gage (2008) algorithm perform best (IWPC: R=50%; Gage: R=49%), and all pharmacogenetic algorithms outperform the IWPC clinical equation (R=22%). VKORC1 and CYP2C9 genotypes did not affect long-term variability in dose. Finally, the Fluidigm platform, a novel warfarin genotyping method, showed 99.65% concordance between different operators and instruments.CYP4F2 and pooled rare variants of CYP2C9 significantly improve the ability to estimate warfarin dose.

Abstract

The majority of patients with systemic mast cell disease express the imatinib-resistant Asp816Val (D816V) mutation in the KIT receptor tyrosine kinase. Limited treatment options exist for aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL). We evaluated whether PKC412, a small-molecule inhibitor of KIT with a different chemical structure from imatinib, may have therapeutic use in advanced SM with the D816V KIT mutation. We treated a patient with MCL (with an associated myelodysplastic syndrome (MDS)/myeloproliferative disorder [MPD]) based on in vitro studies demonstrating that PKC412 could inhibit D816V KIT-transformed Ba/F3 cell growth with a 50% inhibitory concentration (IC50) of 30 nM to 40 nM. The patient exhibited a partial response with significant resolution of liver function abnormalities. In addition, PKC412 treatment resulted in a significant decline in the percentage of peripheral blood mast cells and serum histamine level and was associated with a decrease in KIT phosphorylation and D816V KIT mutation frequency. The patient died after 3 months of therapy due to progression of her MDS/MPD to acute myeloid leukemia (AML). This case indicates that KIT tyrosine kinase inhibition is a feasible approach in SM, but single-agent clinical efficacy may be limited by clonal evolution in the advanced leukemic phase of this disease.